The objective of this research is the elucidation of the action of glucagon, epinephrine, and the glucocorticoid hormones in their roles as regulators of gluconeogenesis. This research will center about the hypothesis proposed by the principal investigator that these hormones stimulate glucose synthesis by enhancing the entrance of pyruvate into hepatic mitochondria. The hypothesis will be tested directly using the inhibitor-stop technique which has proved useful in studies of transport. The metabolism of substrates other than pyruvate is stimulated by glucagon treatment; the transport of these substrates will also be examined for evidence of a generalized enhancement of transport by glucagon. The mechanism by which cyclic adenylic acid mediates the action by glucagon in stimulating mitochondrial metabolism of pyruvate and other substrates will be studied in two ways. A systematic attempt to achieve mitochondrial activation by cyclic adenylic acid in broken cell preparations will be made, and the hypothesis that cyclic acid acts on the mitochondria by controlling protein phosphorylation will be explored.